Objectives. This project intends to train a DVM/PhD clinician-scientist to become an independent scientist and prepare him for a successful career in biomedical science and translational medicine. More specifically, the proposal addresses a knowledge gap in understanding the interactions between endogenous retroviral elements and homologous exogenous horizontally-transmitted retroviral infections. The aims described in this application will investigate molecular and cellular mechanisms conferred by endogenous retroviruses that augment exogenous retroviral infections in a protective and/or detrimental manner. Completion of these studies will provide information of mechanisms that may impact human health. Specific Aims. 1) Characterize exFeLV susceptibility and replication capacity following natural infection of a host without corresponding enFeLV. 2) Determine in vitro FeLV species-specific replication kinetics and relationship to enFeLV proviral loads. 3) Evaluate the impact of enFeLV protein and host cellular receptor expression on in vitro FeLV susceptibility of puma cells. Application to Public Health. Understanding how non-infectious endogenous retroviruses impact human and animal health is important for the potentiation of treatment and prevention of retroviral infections. Endogenous viruses have been shown to play an important part in a well-functioning immune system conferring protection from various infections. However, these interactions are not always beneficial to the host. Some of these endogenous viruses interact with infectious viruses to potentiate exogenous viral infections. The mechanisms by which endogenous retroviruses influence pathogenicity of viral infections has not been widely examined, despite the fact that a significant portion of mammalian DNA is retroviral in origin. This proposal thus proposes studies to understand mechanisms of endogenous-exogenous retroviral interactions and identify therapeutic and virulence factor markers. Research Training Program. This proposal outlines the training program for the applicant as is established by the Colorado State University DVM/PhD medical training program. The applicant will simultaneously complete requirements for a DVM degree while focusing on the requirements to obtain a PhD in the department of Microbiology, Immunology, and Pathology. The goals of the trainee are to complete five publications, a preliminary examination, a dissertation, and requirements for a DVM degree while supported by this fellowship. The goals of the training program will prepare the applicant for a career as an independent clinician-scientist in translational medical field. Successful completion of the training plan will depend on mentorship from the sponsor, cooperation and advice amongst the graduate research advisory committee and other advisors, a well-established DVM/PhD program, a creative and rigorous research plan, and the applicant?s tenacity. Each of these attributes are described in this application.